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Genetics & Diabetes

Genetics may play a role in the development of diabetes for many patients, along with environment and behavior. Scientists have linked several specific genes to the various forms of diabetes.

 

The risks of developing type 1 diabetes, an autoimmune disease, are greater when a parent also has the disease. This factor indicates a probable genetic factor. A single gene that is responsible for type 1 diabetes has not been identified. However, 19 sections of the human genome (complete genetic material) are believed to be involved.

Type 2 diabetes is also highly complex developmentally. It is the most common type of the disease and has the clearest association with genetic inheritance. It may involve multiple genes that cause insulin resistance or that result in loss of insulin being produced by the pancreas. Researchers have found that exercise and weight loss may often prevent type 2 diabetes in people with genetic risk factors.

For other types of diabetes, such as maturity-onset diabetes of the young (MODY), a genetic link is clearly established. There are six types of MODY, each associated with a single genetic defect inherited from a parent. Other diabetic conditions with identified genetic causes include Wolfram syndrome, type A insulin resistance and Rabson-Mendenhall syndrome, which also causes insulin resistance.

About Genetics

It is easier to understand genetics and the link to diabetes by learning some of the basic terms used to study the inheritance of biological characteristics. These include:

  • Chromosomes. Rod-shaped element in the nucleus (center) of each cell. Chromosomes contain the hereditary information that guides all cell actions. A person typically has 46 chromosomes, and one set of 23 chromosomes is inherited from each parent. The sex-determining chromosomes X and Y are two of the 46 chromosomes.

  • Genes. The basic unit of hereditary. Each gene is located in a specific site on a chromosome. Each human cell has about 20,000 to 25,000 genes. A person inherits two copies of each gene, one from each parent. They help determine physical characteristics such as eye color and skin color. Genes also contribute to other characteristics in which environment and behavior play a role, such as body weight, intelligence and the risk of diabetes and other diseases. How genes are involved in diabetes is not clearly understood.

  • Genome. All of the genetic material in an organism’s chromosomes.

  • DNA (deoxyribonucleic acid). A complex substance in genes that contains genetic information needed to make the body’s proteins. These proteins allow the body to function and grow.

 

  • Allele. Variations of a single gene. An individual’s genes have two alleles, one inherited from the mother and one from the father. Differences in alleles are one factor involved in differences among people in physical characteristics and susceptibility to disease.

Genetics and Type 1 Diabetes

Type 1 diabetes is an autoimmune disease, in which the immune system destroys the body’s capacity to produce insulin. Insulin is a hormone that helps cells use glucose (blood sugar) for energy.

Researchers have found many factors that appear to be linked to type 1 diabetes, but there does not seem to be any single cause. Some of the factors include viruses, certain diets, chemicals and other environmental factors. Genetics is also believed to play a role, which is indicated by the disease occurring multiple times in a family.

A family history of type 1 diabetes is a major indicator that a person may also develop the disorder. The risk of a child developing type 1 diabetes in association with a parent with the disease is the following:

  • 1 in 17 when the father has diabetes

  • 1 in 25 when the mother has diabetes and gave birth to the child before age 25

  • 1 in 100 when the mother has diabetes and gave birth to the child after age 25

  • 1 in 4 to 1 in 10 when both parents have diabetes

For each of these figures, the risk of diabetes doubles if the parent developed the disease before age 11.

The high rate of occurrence of diabetes within families helped encourage research into genetic links to the disease. Scientists are trying to determine which genes are involved in individuals with type 1 diabetes and how genetic mutations interfere with the production of insulin. To date, they have not found a single gene responsible for type 1 diabetes. However, there are about 19 sections of the human genome that appear to be related to a susceptibility to type 1 diabetes.

One section of the genome contains several genes involved in building human leukocyte antigens (HLA). The proteins formed by these genes help the immune system recognize the body’s own cells. When HLA genes malfunction, an autoimmune disorder may occur.

There are many types (alleles) of HLA genes. According to the American Diabetes Association, 95 percent of people with type 1 diabetes have HLA-DR3, HLA-DR4 or both alleles. The HLA genes involved in diabetes also vary by ethnicity and race. HLA-DR3 and HLA-DR4 are most common in white diabetic patients, but HLA-DR7 is common in patients of African descent and HLA-DR9 is common in patients of Japanese descent.

The inherited HLA-DR gene makes individuals more susceptible to type 1 diabetes, but it is not the only factor. Other genes, including other HLA genes (HLA-DQ) and IDDM2 (the insulin gene), are also likely to be involved. Researchers are continuing to study additional gene clusters and chromosomes to determine their role in type 1 diabetes.

The genetic factor is a complicated issue in the development of type 1 diabetes. Most people with the disease do not have a parent or sibling with it. Also, identical twins have identical genes, but there is only a 50 percent chance of both twins developing the disease. This means that factors in addition to genetics play a role in the development of the disease.

A form of type 1 diabetes that can develop in adults is known as latent autoimmune diabetes of adulthood (LADA). It is not known how the genetic risk factors for LADA may differ from those of standard type 1 diabetes.

Genetics and Type 2 Diabetes

Type 2 diabetes is a condition in which the body resists the insulin produced by the pancreas and may fail to make enough insulin to maintain normal glucose (blood sugar) levels. It is by far the most common form of diabetes.

          

A genetic link to type 2 diabetes appears much stronger than for type 1. Identical twins share the same genetic code, but should one identical twin develop type 2 diabetes, the risk for the other twin is 60 to 75 percent, according to the American Diabetes Association.

Evidence for the genetic basis of the disease is also provided by its frequency among racial and ethnic groups. In the United States, type 2 diabetes occurs most frequently among African Americans, Hispanics/Latinos, Native Americans, Alaska Natives, Asian Americans and Pacific Islanders.

Some researchers believe that this prevalence is due to the presence of a “thrifty” gene or set of genes inherited amongst these ethnic groups. In theory, the thrifty gene originally altered the use of insulin to enable people to store energy in the body more efficiently to survive periods of food scarcity. Surviving food scarcity periods is generally no longer an issue in modern Western societies, and the thrifty gene has shifted from being a survival mechanism to being a risk factor for diabetes.

Research indicates that in most cases of type 2 diabetes there is more than one gene involved and that the gene combinations may differ between families. In addition, the genes may have only slight variations, and it is possible that the variations are common in the human population. These factors make research into the genetics of type 2 diabetes difficult.

These genes appear to affect the way insulin acts on tissues, creating insulin resistance. This condition impairs the ability of cells to use the insulin that is present, and it accumulates in the bloodstream, causing hyperinsulinemia. In addition, other genes may affect the insulin-making beta cells of the pancreas, limiting their ability to produce enough insulin to overcome the resistance.

Scientists in recent years have linked several genes to development of type 2 diabetes. For example:

  • A gene variant called TCF7L2 could predispose close to 38 percent of Northern European populations and many black Americans to type 2 diabetes. It might increase their risk of diabetes by 80 percent. However, these researchers found that moderate exercise and weight loss the same preventive treatments touted in the landmark Diabetes Prevention Program could virtually erase the additional risk in people with this genetic makeup.

  • A gene called ARNT (aryl hydrocarbon receptor nuclear translocator) has been found to be expressed abnormally in the beta cells of people with type 2 diabetes. The discovery provides new insight into the development of the disease, and potentially a treatment.

The identification of some genes involved in type 2 diabetes has led to the development of genetic tests for the disease. These tests examine samples of blood or cells from the inside of the cheek for the responsible gene. Interpreting the results is complicated, and genetic counseling is recommended to patients interested in undergoing genetic screening.

Genetics can also contribute to factors that may lead to type 2 diabetes. Obesity, which is caused by both genetic and environmental factors, increases insulin resistance and the risk of type 2. Other risk factors for type 2 diabetes that may involve a genetic component include:

  • Unhealthy levels of cholesterol and triglycerides (hyperlipidemia)
  • Metabolic syndrome
  • High blood pressure

Though a family history of type 2 diabetes is one of the strongest risk factors for developing the disease, this genetic predisposition is far more significant for those who consume an unhealthy, high-calorie diet and get little exercise.

Gestational diabetes, the form that affects some women during pregnancy, is also a metabolic disorder and may have a similar genetic composition to type 2 diabetes.

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